The developmental timing of the increase in the rate and the emergence of sex differences in depression points to adolescence as a critical period for understanding the causal mechanisms underlying the development of depressive disorders in females. Adolescent neural development is likely to play a key role in the etiology of depression, but little is known about the interface between the development of neural circuitry and depression across adolescence. In response to PA-09-108 Women's Mental Health and Sex/Gender Differences Research, we will determine if developmental changes in the neural circuitry engaged by emotionally evocative stimuli are related to adolescent depression in girls. Mapping developmental trajectories of depression symptoms onto relevant neural systems will further our understanding of the maturational changes in brain function that contribute to age-related vulnerability. Investigators: Drs. Keenan, Guyer and Forbes are the PIs;they began collaborating on the neuroscience of depression two years ago. Dr. Kevin Grimm, a statistician specializing in longitudinal modeling, and Dr. Alison Hipwell an expert in female mental health, are Co- Investigators. Consultants are Drs. Gang Chen, Ronald Dahl, Constance Hammen, and Daniel Pine. Innovation: Brain-behavior perturbations in information processing are a major focus of clinical neuroscience research. Developmental shifts in neural circuits during adolescence are critical to understanding the emergence of psychopathology during this period. No study to date, however, has been designed to test the hypothesis that development of the functional connections between affective and cognitive circuits during the adolescent period is related to depression-onset, or to characterize the patterns of neural development that in fact confer risk for depression onset. Approach: This proposal builds on a recently completed NIMH-funded study of precursors to depression in girls, in which depression symptoms and negative life events were documented from ages 9-14. Half of the sample was selected on measures indicative of high risk for developing depressive disorders. For this PA, we propose to study this sample from ages 15-19 years and to conduct annual assessments of depression and environmental stressors and annual assessments of emotional memory and reward processing using neuroimaging. Developmental patterns in functional connectivity between amygdala-ventral-lateral prefrontal cortex (vlPFC) circuitry and striatum-medial prefrontal cortex (mPFC) circuitry during memory for emotional faces and reward processing, respectively, will be captured across four time points, as will environmental stress exposure. Environment: This proposal involves a multi-institutional investigation at the Universities of Chicago, Pittsburgh, and California-Davis. Assessments of depression, stress exposure, and brain function will be conducted in the University of Pittsburgh's Department of Psychiatry and the Neuroimaging of Emotional Disorders Lab at Western Psychiatric Institute and Clinic, which is internationally recognized for research on brain functioning and child psychopathology. PUBLIC HEALTH RELEVANCE: We propose to determine if developmental changes in how the brain responds to emotional stimuli during adolescence can inform us regarding which girls are at risk for developing depressive disorders. Adolescence appears to be a time of vulnerability in terms of developing circuits in the brain that help regulate emotional responses. By conducting a longitudinal study from ages 15-19 we will be able to examine individual differences in brain functioning from mid to late adolescence and test whether different pathways to developing mature brain circuits explains individual differences in risk for depression.